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8-K – Current report

On November 11, 2014 Threshold Pharmaceuticals reported that the U.S. Food and Drug Administration (FDA) granted Fast Track designation for TH-302, an investigational anticancer drug, for the treatment of previously untreated patients with metastatic or locally advanced unresectable soft tissue sarcoma (STS) (Filing 8-K , Threshold Pharmaceuticals, NOV 12, 2014, View Source [SID:1234500955]).

The FDA established the Fast Track designation process to facilitate the development and expedite the review of drugs intended to treat serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs. An important feature of Fast Track is that the FDA may consider a “rolling review” of completed sections of the New Drug Application (NDA) before the complete application is submitted.

“We are pleased that FDA has granted Fast Track status for TH-302 for the treatment of previously untreated patients with metastatic or locally advanced unresectable soft tissue sarcoma,” said Barry Selick, Ph.D., Chief Executive Officer of Threshold. “Our ongoing Phase 3 trial of TH-302 in these patients is being conducted under a Special Protocol Assessment with the FDA. If successful, the Fast Track designation may provide an added benefit of facilitating the NDA review process. Currently, we anticipate the primary analysis of overall survival of the Phase 3 trial to be conducted in the first quarter of 2016.”

About the Phase 3 Trial

Threshold is conducting this international, randomized pivotal Phase 3 clinical trial in partnership with the Sarcoma Alliance for Research through Collaboration (SARC) and under a Special Protocol Assessment (SPA) agreement with the U.S. FDA. The trial is designed to investigate the efficacy and safety of TH-302 in combination with doxorubicin, compared with doxorubicin alone, in previously untreated patients with metastatic or locally advanced unresectable STS. The primary endpoint of the trial is overall survival. Secondary endpoints include progression-free survival, overall response rate, pharmacokinetics and safety. Patients were randomized to either doxorubicin alone or to receive TH-302 300 mg/m2 administered intravenously on Days 1 and 8 with doxorubicin 75 mg/m2 on Day 1 of each 21-day cycle. After six cycles, patients with stable and/or responding disease could receive maintenance monotherapy with TH-302 according to the same dosing schedule, 300 mg/m2 Days 1 and 8 of each 21-day cycle. The trial enrolled a total of 640 patients across 81 study sites in Europe, Israel, North America and the Russian Federation.

Patrys to Initiate Clinical Trial with Onyx Pharmaceuticals

On November 11, 2013 Patrys reported that it is initiating an investigator-sponsored trial (IST) evaluating the effectiveness of Patrys’ lead anti-cancer drug PAT-SM6 in combination with carfilzomib, in patients with relapsed and refractory multiple myeloma (MM) (Press release Patrys, NOV 11, 2014, View Source [SID:1234500543]). The trial will be headed by Professor Dr. Hermann Einsele, Director of the Department of Medicine II, University of Würzburg, Germany, and is being funded by Onyx Pharmaceuticals, Inc., an Amgen subsidiary.
Both clinical and preclinical studies of PAT-SM6 conducted to date have shown evidence of activity in patients with relapsed and refractory MM. One of the notable features of PAT-SM6, being demonstrated in the currently-ongoing Phase I/IIa clinical trial, is the lack of serious side-effects in treated patients. This feature of PAT-SM6 may allow it to be safely administered in combination with carfilzomib and may have the potential to improve current treatments for MM. Carfilzomib is a proteasome inhibitor owned by Onyx, and is marketed in the United States (U.S.) under the brand name Kyprolis (carfilzomib) for Injection. Onyx will provide carfilzomib study drug for the trial.

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10-Q – Quarterly report [Sections 13 or 15(d)]

Dendreon has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission .

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(Press release, EnGeneIC, NOV 10, 2014, View Source [SID:1234504550])

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8-K – Current report

On November 10, 2014 OXiGENE reported the first presentation at a scientific conference of the positive results from the Phase 2 GOG 186I study of fosbretabulin combined with bevacizumab in recurrent ovarian, tubal and peritoneal carcinoma (Filing 8-K , OXiGENE, NOV 10, 2014, View Source [SID:1234500958]). The detailed data were presented by the Gynecologic Oncology Group (GOG), now part of NRG Oncology, in an oral presentation at the 15th Biennial Meeting of the International Gynecologic Cancer Society (IGCS) meeting held in Melbourne, Australia.

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The study achieved its primary endpoint and demonstrated a statistically significant increase in progression-free survival (PFS) for the combination as compared to bevacizumab alone (p=0.049; HR=0.685). The study enrolled 107 patients with both platinum-sensitive and platinum-resistant recurrent ovarian cancer at 67 clinical sites in the United States. Median PFS was 7.3 months for bevacizumab plus fosbretabulin (n=54) compared to 4.8 months with bevacizumab (n= 53).

"This is the first randomized trial to demonstrate a potential clinical benefit from the combination of a vascular disrupting agent with an anti-angiogenic agent in ovarian cancer," said Bradley J. Monk, M.D., FACS, FACOG, principal investigator for the trial, and Professor and Director, Division of Gynecologic Oncology and Department of Obstetrics and Gynecology at the University of Arizona Cancer Center. "Given the significant need for new treatment options in recurrent ovarian cancer, we are extremely encouraged by the results of this study that combine two anti-vascular agents without chemotherapy. We believe that additional evaluation of the benefits of combined fosbretabulin and bevacizumab in ovarian cancer patients is strongly warranted."

In a post-hoc subgroup analysis, data showed that patients who were platinum-resistant also had a statistically significant improvement in PFS with the combination. Among these 27 patients, median PFS was 6.7 months for those on bevacizumab and fosbretabulin compared to 3.4 months for those receiving bevacizumab alone (p=0.01; HR=0.57). Although the subgroup included a relatively small number of patients, these findings suggest that adding fosbretabulin to bevacizumab has a potentially greater effect in this difficult-to-treat patient group than for platinum-sensitive patients.

"We believe that these compelling data show fosbretabulin has a meaningful benefit in recurrent ovarian cancer, particularly in platinum-resistant patients who have extremely limited treatment options," said Dai Chaplin, Ph.D., OXiGENE’s President and CEO. "We now look forward to discussing these findings with the regulatory agencies to determine a potential path forward for fosbretabulin in ovarian cancer."

Patients with measurable disease who received the combination of fosbretabulin and bevacizumab may achieve a higher objective response rate (ORR), a secondary endpoint in the study measured according to RECIST criteria. Although not a statistically significant result, patients receiving the combination had an ORR of 35.7 percent (n=42) compared to 28.2 percent for patients on bevacizumab alone (n=39). In the small subgroup of platinum-resistant patients, the addition of fosbretabulin to bevacizumab treatment increased ORR to 40 percent (n=10) compared to 12.5 percent (n=8) for bevacizumab.

Additional secondary endpoints in the study included safety and overall survival. All treatment- related adverse events in the study were manageable, with one Grade 4 event occurring in each treatment arm. Consistent with prior clinical experience with fosbretabulin, patients in the combination arm experienced an increased incidence of Grade 3 hypertension compared to the control arm (10 cases for bevacizumab as compared to 17 for the combination). All cases of hypertension were managed with antihypertensive treatments, as specified in the study protocol.

Patients continue to be followed for overall survival. A preliminary analysis of 33 events did not demonstrate a difference in overall survival between the study arms. Further analysis of this secondary endpoint will be conducted as the data matures.